PSEUDOMONAS SIDEROPHORE PYOCHELIN ENHANCES NEUTROPHIL-MEDIATED ENDOTHELIAL-CELL INJURY

Pyochelin, a siderophore secreted by Pseudomonas aeruginosa, binds iro n in a form which can catalyze the formation of hydroxyl radical (.OH) from neutrophil-derived superoxide (O-2(-).) and hydrogen peroxide (H 2O2) Ferripyochelin induced a concentration-dependent increase in endo thelial cell injury (Cr-51 release) resulting from exposure to H2O2, a xanthine/xanthine oxidase O-2(-)./H2O2 generating system, or stimulat ed neutrophils. This process was dependent on the presence of iron. Fo rmation of OH was confirmed using spin trapping. Although a slight (13 %) increase in neutrophil O-2(-). production in the presence of ferrip yochelin was observed, this did not appear to account for the extent o f endothelial cell injury observed. The antioxidants dimethylthiourea and catalase decreased endothelial cell injury, whereas dimethyl sulfo xide and superoxide dismutase were without effect. Fe-nitrilotriacetic acid and Fe-EDTA, which are also OH catalysts, did not augment endoth elial cell injury resulting from exposure to the above oxidant systems . In contrast to results with the endothelial cells, killing of P. aer uginosa by O-2(-)./H2O2 derived from the reaction of xanthine and xant hine oxidase was not increased by ferripyochelin. These data are consi stent with the possibility that the interaction of Pseudomonas- and ph agocyte-derived secretory products could contribute to local tissue in jury at sites of P. aeruginosa infection by causing the generation of .OH.